Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study.
BACKGROUND
Clinical trials in children with moderate-to-severe persistent asthma are limited.


OBJECTIVE
We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing.


METHODS
The budesonide dose (with salmeterol [50 microg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 microg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction.


RESULTS
Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated.


CONCLUSIONS
Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma.
Strunk
Robert C
RC
Department of Pediatrics, Washington University and St Louis Children's Hospital, St Louis, MO 63110, USA. strunk@kids.wustl.edu
Bacharier
Leonard B
LB
Phillips
Brenda R
BR
Szefler
Stanley J
SJ
Zeiger
Robert S
RS
Chinchilli
Vernon M
VM
Martinez
Fernando D
FD
Lemanske
Robert F
RF
Taussig
Lynn M
LM
Mauger
David T
DT
Morgan
Wayne J
WJ
Sorkness
Christine A
CA
Paul
Ian M
IM
Guilbert
Theresa
T
Krawiec
Marzena
M
Covar
Ronina
R
Larsen
Gary
G
D000085:Acetates / Q000008:administration & dosage*; D000293:Adolescent; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D017963:Azithromycin / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D011804:Quinolines / Q000008:administration & dosage*; D000068299:Salmeterol Xinafoate; D012720:Severity of Illness Index; D013440:Sulfides; D013997:Time Factors
D000085:Acetates; D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D005938:Glucocorticoids; D011804:Quinolines; D013440:Sulfides; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D017963:Azithromycin; C093875:montelukast; D000420:Albuterol